Eyeworld

EW NEWS & OPINION 44 April 2016 by Liz Hillman EyeWorld Staff Writer Decline in key lens protein leads to nuclear cataracts similar way to alpha-crystallin and administering it to patients as their own finite amount of alpha-crystal- lin becomes used up. He also said gene therapy could be a possible avenue. "We could introduce genes that favor the production of maximum amounts of alpha-crystallins or find substances that would stimulate the production of alpha-crystallins in the lens," he said. Dr. Mamalis said the long-term implications of this DLS research are important for those trying to better understand the causes of cataracts and their prevention. "One of the difficulties we've had in the past when we're looking at something that's going to try to prevent a cataract is how do you objectively grade cataracts? What we've had to use in the past is a series of photographs of the nucleus, the cortex, and the posterior subcap- sular area and then rate it depending on what we see when we look at the slit lamp," he said. "This technology is a much more sophisticated way of measuring changes within the lens of the eye that could lead to cata- racts." EW References 1. Datiles MB, et al. Longitudinal study of age-related cataract using dynamic light scattering: loss of a-crystallin leads to nuclear cataract development. Ophthalmology. 2016;123(2):248–54. 2. Ansari RR, et al. Measuring lens opacity: combining quasi-elastic light scattering with Scheimpflug imaging system. Proc. SPIE 3246, Ophthalmic Technologies VIII, 1 June 1998. 3. Datiles MB, et al. Clinical detection of early precataractous lens protein changes using dynamic light scattering. Arch Ophthalmol. 2008;126:1687–93. Editors' note: The sources have no financial interests related to their comments. Contact information Datiles: datilesm@nei.nih.gov Mamalis: nick.mamalis@hsc.utah.edu document and track the formation of cataracts. Around the same time, Rafat Ansari, PhD, John H. Glenn Re- search Center, NASA, was working on DLS technology that would be used to conduct fluid physics exper- iments on the International Space Station, Dr. Datiles said. Doing his own literature re- search to help his father, who had developed cataracts, Dr. Ansari came across Dr. Datiles' work. The 2 even- tually found they had a lot in com- mon, not only with their interest in cataracts, but with the technology they were pursuing. The pair decided to compare a machine Dr. Datiles was working with (the Scheimpflug cataract camera, Carl Zeiss Meditec, Jena, Germany) to one Dr. Ansari had helped create for NASA to measure cold cataract formation in calf lens- es. Dr. Datiles said the DLS machine that Dr. Ansari used "won hands down" and could detect changes in the lens well before his machine could pick up anything. 2 From there, Dr. Datiles said they secured funding from their respective agencies to develop a DLS machine that was safe to use on human patients in order to track the changes in alpha-crystallin levels. While DLS techniques have been around as early as the 1970s to study lens proteins of the eye, the technology was very large and unwieldy, Dr. Datiles said. Similar research looked at the proteins that aggregate to form cataracts but not alpha-crystallin. NASA created a DLS machine small enough to fit inside of a shoebox, which Dr. Datiles and Dr. Ansari modified further to use in vivo and with technology that would allow it to measure protein levels at a controlled, specific depth over and over again. "Patients were very happy with it," Dr. Datiles said of the experience with the machine. "Patients said that this was nothing compared to the flash when you take a picture." The study After an earlier clinical cross-section- al study of nearly 400 eyes that had a range of nuclear cataract opacities found lower alpha-crystallin levels were associated with a greater opaci- ty, 3 the team conducted this longitu- dinal study using 45 patients 34–79 years old. The alpha-crystallin levels in these patients was measured every 6 months for a mean of 19 months. Dr. Datiles said that as alpha- crystallin levels neared zero, the cataract became visible "because there is nothing to prevent the lens particles from sticking together, becoming big particles and causing clouding." Nick Mamalis, MD, professor of ophthalmology, John A. Moran Eye Center, University of Utah, Salt Lake City, who was not involved in the research, said that correlation was particularly interesting. "What they found was that the patients who had the lowest base- line levels of [alpha-crystallin index] (ACI) over time had the most rapid progression of cataracts and that the lenses of people with higher ACI as a baseline had either no or slow pro- gression of cataracts," Dr. Mamalis said. "They not only found in their studies that the alpha-crystallin lev- els are related to cataract formation, but they measured in a group of patients and followed them out for greater than a year and a half, and they found that it did correlate with the progression of the cataracts. I think that's an important finding." Dr. Datiles said the research "es- sentially confirmed the fact that in this most common type of cataract, the cause is loss of alpha-crystallin." "When you're studying a disease, once you find the cause, it becomes easier to find the cure," he said. Implications for cataract research Armed with this knowledge, Dr. Datiles said further research could focus on finding or creating a mini-chaperone that works in a NASA technology refined to measure alpha-crystallin in vivo, providing new avenue for early cataract detection A recent study confirmed previous research that suggested loss of the lens protein alpha-crystallin leads to nuclear cataract development. This finding—and the method the study authors used to measure alpha-crystallin levels —has important implications for better understanding the etiology of cataract formation and for further- ing other cataract prevention and treatment research. The longitudinal study pub- lished in Ophthalmology used a dynamic light scattering (DLS) tech- nique to safely measure levels of al- pha-crystallin in the lens of human patients in vivo. 1 Alpha-crystallin has molecular chaperone properties and binds to other lens proteins that have a tendency to fold, clump, and thus form opacities. Alpha-crystal- lin binding to these other proteins stabilizes them and prevents them from aggregating. The catch is peo- ple are born with a finite amount of alpha-crystallin; once it is used up, cataract formation can occur. Using DLS technology devel- oped by the National Eye Institute (NEI) and NASA, researchers were able to determine that as free, un- bound alpha-crystallin levels in the lens decline, opacity risk increases. "The ability of the DLS device to measure unbound alpha-crystallin in the lens in vivo while the lens is still clear potentially opens up new avenues for lens research, includ- ing for presbyopia, which has been linked to alpha-crystallin age-related changes," the study authors wrote. Using space technology on the eye In the 1990s, Manuel Datiles III, MD, medical officer and senior clinical investigator, NEI, was part of a team searching for a cataract cure. His work specifically involved the development of clinical methods to

• Cover